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Article ; Online: Comparison of antioxidant properties of different therapeutic albumin preparations.

Plantier, Jean-Luc / Duretz, Véronique / Devos, Véronique / Urbain, Rémi / Jorieux, Sylvie

Biologicals : journal of the International Association of Biological Standardization

2016 Volume 44, Issue 4, Page(s) 226–233

Abstract: Albumin displays several important functions for homeostasis amongst which the maintenance of the plasma redox-state. The study aim was to compare the redox state of pharmaceutical human albumin preparations since it reflects the oxidation-reduction ... ...

Abstract	Albumin displays several important functions for homeostasis amongst which the maintenance of the plasma redox-state. The study aim was to compare the redox state of pharmaceutical human albumin preparations since it reflects the oxidation-reduction status of the surrounding environment. Using an array of analytical methods, four commercially available albumins were compared with respect to their structural characteristics (cobalt ion binding, glycation, spectrophotometric and fluorometric profiles) and their ability to scavenge hydroxyl, peroxyl or free radicals. The different albumins exhibited a similar structural profile as well as hydroxyl and peroxyl scavenging activities. By contrast, the albumin from LFB (Vialebex(®)) possessed a significantly higher capacity to transfer electrons to DPPH, as compared with other albumins that was correlated with the level of free cysteine-34. Commercially available albumins differed for some of their antioxidant properties. The albumin preparation possessing the highest level of free cysteine-34 exhibited the highest antioxidant potential.
MeSH term(s)	Antioxidants/chemistry ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Biphenyl Compounds/chemistry ; Cysteine/chemistry ; Free Radical Scavengers/chemistry ; Free Radical Scavengers/pharmacology ; Free Radical Scavengers/therapeutic use ; Free Radicals/antagonists & inhibitors ; Free Radicals/metabolism ; Glycosylation ; Humans ; Hydroxyl Radical/antagonists & inhibitors ; Hydroxyl Radical/metabolism ; Oxidation-Reduction/drug effects ; Picrates/chemistry ; Serum Albumin/chemistry ; Serum Albumin/pharmacology ; Serum Albumin/therapeutic use ; Spectrophotometry
Chemical Substances	Antioxidants ; Biphenyl Compounds ; Free Radical Scavengers ; Free Radicals ; Picrates ; Serum Albumin ; Hydroxyl Radical (3352-57-6) ; 1,1-diphenyl-2-picrylhydrazyl (DFD3H4VGDH) ; Cysteine (K848JZ4886)
Language	English
Publishing date	2016-07
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	1017370-5
ISSN	1095-8320 ; 1045-1056
ISSN (online)	1095-8320
ISSN	1045-1056
DOI	10.1016/j.biologicals.2016.04.002
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Article ; Online: Characterization of monoclonal antibodies by a fast and easy liquid chromatography-mass spectrometry time-of-flight analysis on culture supernatant.

Henninot, Antoine / Terrier, Aurelie / Charton, Julie / Urbain, Rémi / Fontayne, Alexandre / Deprez, Benoit / Beghyn, Terence

Analytical biochemistry

2015 Volume 491, Page(s) 52–54

Abstract: Rapid and efficient structural analysis is key to the development of new monoclonal antibodies. We have developed a fast and easy process to obtain mass spectrometry profiles of antibodies from culture supernatant. Treatment of the supernatant with IdeS ... ...

Abstract	Rapid and efficient structural analysis is key to the development of new monoclonal antibodies. We have developed a fast and easy process to obtain mass spectrometry profiles of antibodies from culture supernatant. Treatment of the supernatant with IdeS generates three fragments of 25 kDa that can be analyzed by liquid chromatography-mass spectrometry time-of-flight (LC-MS TOF) in one run: LC, Fd, and Fc/2. This process gives rapid access to isoform and glycoform profiles. To specifically measure the fucosylation yield, we included a one-pot treatment with EndoS that removes the distal glycan heterogeneity. Our process was successfully compared with high-performance capillary electrophoresis with laser-induced fluorescence detection (HPCE-LIF), currently considered as the "gold standard" method.
MeSH term(s)	Antibodies, Monoclonal/analysis ; Chromatography, High Pressure Liquid ; Electrophoresis, Capillary ; Glycosylation ; Protein Isoforms/analysis ; Spectrometry, Fluorescence ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Chemical Substances	Antibodies, Monoclonal ; Protein Isoforms
Language	English
Publishing date	2015-12-15
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1110-1
ISSN	1096-0309 ; 0003-2697
ISSN (online)	1096-0309
ISSN	0003-2697
DOI	10.1016/j.ab.2015.08.006
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Article: Les anticorps EMABling(R) : De la prophylaxie de l'allo-immunisation foeto-maternelle au traitement de la leucémie lymphoïde chronique.

Urbain, Rémi / Teillaud, Jean-Luc / Prost, Jean-François

Medecine sciences : M/S

2009 Volume 25, Issue 12, Page(s) 1141–1144

Abstract: The Laboratoire français du fractionnement et des biotechnologies (LFB), the leading manufacturer of plasma-derived medicinal products in France and 6th worldwide, is strongly involved in the development of therapeutic monoclonal antibodies (mAb). For ... ...

Title translation	EMABling antibodies: from feto-maternal allo-immunisation prophylaxis to chronic lymphocytic leukaemia therapy.
Abstract	The Laboratoire français du fractionnement et des biotechnologies (LFB), the leading manufacturer of plasma-derived medicinal products in France and 6th worldwide, is strongly involved in the development of therapeutic monoclonal antibodies (mAb). For more than 15 years, LFB has been focusing its research effort on the study of structure-function relationship of antibodies. Its studies on the molecular basis of IgG interaction with the receptors for the Fc portion of IgG (FcgRs) has made it possible to develop antibodies with high antibody-dependent cellular cytotoxicity (ADCC) activity and enhanced affinity to FcgRIII (CD16), both correlated to a glycosylation pattern characterized by a low fucose content. Based on these studies, LFB has developed EMABling, a technological platform for the production of antibodies with enhanced cytotoxicity ability. Two EMABling antibodies recently entered clinical development: LFB-R593, a fully human anti-rhesus D (RhD) antibody, for the prevention of feto-maternal allo-immunization in RhD- women, as a substitute for human polyclonal anti-RhD immunoglobulins, and LFB-R603, a monoclonal antibody directed against CD20, for the treatment of B cell malignancies. LFB investment in bioproduction through the recent acquisition of MAbgène company, a fully integrated French contract biopharmaceutical manufacturing company, allows the production of antibodies to a large GMP scale. As a whole, LFB owns a portfolio of several EMABling antibodies with high therapeutic interest, in line with its public health mission.
MeSH term(s)	Animals ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/isolation & purification ; Antibodies, Monoclonal/therapeutic use ; Antibody-Dependent Cell Cytotoxicity ; Antineoplastic Agents/immunology ; Antineoplastic Agents/therapeutic use ; Drug Industry/organization & administration ; Female ; France ; Glycosylation ; Humans ; Immunoglobulin G/immunology ; Infant, Newborn ; Isoantibodies/isolation & purification ; Isoantibodies/therapeutic use ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Macaca fascicularis ; Pregnancy ; Protein Processing, Post-Translational ; Receptors, IgG/immunology ; Rh Isoimmunization/prevention & control ; Rho(D) Immune Globulin ; Technology, Pharmaceutical
Chemical Substances	Antibodies, Monoclonal ; Antineoplastic Agents ; Immunoglobulin G ; Isoantibodies ; LFB-R593 ; LFB-R603 ; RHO(D) antibody ; Receptors, IgG ; Rho(D) Immune Globulin
Language	French
Publishing date	2009-12
Publishing country	France
Document type	English Abstract ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/200925121141
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Article ; Online: A capillary zone electrophoresis method to detect conformers and dimers of antithrombin in therapeutic preparations.

Marie, Anne-Lise / Tran, Nguyet Thuy / Saller, François / Abdou, Youmna Mohamed / Zeau, Pascal / Plantier, Jean-Luc / Urbain, Rémi / Borgel, Delphine / Taverna, Myriam

Electrophoresis

2016 Volume 37, Issue 12, Page(s) 1696–1703

Abstract: Antithrombin (AT) is a human plasma glycoprotein that possesses anticoagulant and anti-inflammatory properties. However, the native (active) form of AT is unstable and undergoes conformational changes, leading to latent, cleaved, and heterodimeric forms. ...

Abstract	Antithrombin (AT) is a human plasma glycoprotein that possesses anticoagulant and anti-inflammatory properties. However, the native (active) form of AT is unstable and undergoes conformational changes, leading to latent, cleaved, and heterodimeric forms. The presence of these alternative forms mostly inactive can highly impact the quality and therapeutic activity of pharmaceutical AT preparations. We developed a capillary zone electrophoresis method, based on a neutral polyethylene oxide-coated capillary and a buffer close to physiological conditions, enabling the separation of more than eight forms of AT. Several peaks were identified as native, latent, and heterodimeric forms. The CZE method was reproducible with intraday relative standard deviations less than 0.5 and 2% for migration times and peak areas, respectively. The method was applied to the comparison of AT preparations produced by five competitive pharmaceutical companies, and statistical tests were performed. Important differences in the proportion of each form were highlighted. In particular, one AT preparation was shown to contain a high quantity of heterodimer, and two preparations contained high quantities of latent form. In addition, one AT preparation exhibited additional forms, not yet identified.
MeSH term(s)	Antithrombin III/isolation & purification ; Buffers ; Dimerization ; Drug Compounding ; Electrophoresis, Capillary/instrumentation ; Electrophoresis, Capillary/methods ; Polyethylene Glycols ; Protein Conformation ; Protein Isoforms/isolation & purification
Chemical Substances	Buffers ; Protein Isoforms ; Polyethylene Glycols (30IQX730WE) ; Antithrombin III (9000-94-6)
Language	English
Publishing date	2016
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	619001-7
ISSN	1522-2683 ; 0173-0835
ISSN (online)	1522-2683
ISSN	0173-0835
DOI	10.1002/elps.201500456
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Article: Selection of IgG Variants with Increased FcRn Binding Using Random and Directed Mutagenesis: Impact on Effector Functions.

Monnet, Céline / Jorieux, Sylvie / Urbain, Rémi / Fournier, Nathalie / Bouayadi, Khalil / De Romeuf, Christophe / Behrens, Christian K / Fontayne, Alexandre / Mondon, Philippe

Frontiers in immunology

2015 Volume 6, Page(s) 39

Abstract: Despite the reasonably long half-life of immunoglogulin G (IgGs), market pressure for higher patient convenience while conserving efficacy continues to drive IgG half-life improvement. IgG half-life is dependent on the neonatal Fc receptor (FcRn), which ... ...

Abstract	Despite the reasonably long half-life of immunoglogulin G (IgGs), market pressure for higher patient convenience while conserving efficacy continues to drive IgG half-life improvement. IgG half-life is dependent on the neonatal Fc receptor (FcRn), which among other functions, protects IgG from catabolism. FcRn binds the Fc domain of IgG at an acidic pH ensuring that endocytosed IgG will not be degraded in lysosomal compartments and will then be released into the bloodstream. Consistent with this mechanism of action, several Fc-engineered IgG with increased FcRn affinity and conserved pH dependency were designed and resulted in longer half-life in vivo in human FcRn-transgenic mice (hFcRn), cynomolgus monkeys, and recently in healthy humans. These IgG variants were usually obtained by in silico approaches or directed mutagenesis in the FcRn-binding site. Using random mutagenesis, combined with a pH-dependent phage display selection process, we isolated IgG variants with improved FcRn-binding, which exhibited longer in vivo half-life in hFcRn mice. Interestingly, many mutations enhancing Fc/FcRn interaction were located at a distance from the FcRn-binding site validating our random molecular approach. Directed mutagenesis was then applied to generate new variants to further characterize our IgG variants and the effect of the mutations selected. Since these mutations are distributed over the whole Fc sequence, binding to other Fc effectors, such as complement C1q and FcγRs, was dramatically modified, even by mutations distant from these effectors' binding sites. Hence, we obtained numerous IgG variants with increased FcRn-binding and different binding patterns to other Fc effectors, including variants without any effector function, providing distinct "fit-for-purpose" Fc molecules. We therefore provide evidence that half-life and effector functions should be optimized simultaneously as mutations can have unexpected effects on all Fc receptors that are critical for IgG therapeutic efficacy.
Language	English
Publishing date	2015
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2015.00039
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Article: Capillary zone electrophoresis and capillary electrophoresis-mass spectrometry for analyzing qualitative and quantitative variations in therapeutic albumin

Marie, Anne-Lise / Przybylski, Cédric / Gonnet, Florence / Daniel, Régis / Urbain, Rémi / Chevreux, Guillaume / Jorieux, Sylvie / Taverna, Myriam

Analytica chimica acta. 2013 Oct. 24, v. 800

2013

Abstract: The present study describes a reproducible and quantitative capillary zone electrophoresis (CZE) method, which leads to the separation of nine forms (native, oxidized and glycated) of human serum albumin (HSA). In an attempt to identify the different ... ...

Abstract	The present study describes a reproducible and quantitative capillary zone electrophoresis (CZE) method, which leads to the separation of nine forms (native, oxidized and glycated) of human serum albumin (HSA). In an attempt to identify the different species separated by this CZE method, the capillary electrophoresis was coupled to mass spectrometry using a sheath liquid interface, an optimized capillary coating and a suitable CE running buffer. CE-MS analyses confirmed the heterogeneity of albumin preparation and revealed new truncated and modified forms such as Advanced Glycation End products (AGEs). Assignment of the CZE peaks was carried out using specific antibodies, carboxypeptidase A or sample reduction before or during the CE separation. Thus, five HSA forms were unambiguously identified. Using this CZE method several albumin batches produced by slightly different fractionation ways could be discriminated. Furthermore, analyses of HSA preparations marketed by five pharmaceutical industries revealed that two therapeutic albumins, including that marketed by LFB, contained the highest proportion of native form and lower levels of oxidized forms.
Keywords	advanced glycation end products ; antibodies ; capillary zone electrophoresis ; carboxypeptidase A ; coatings ; fractionation ; human serum albumin ; mass spectrometry ; pharmaceutical industry
Language	English
Dates of publication	2013-1024
Size	p. 103-110.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	1483436-4
ISSN	1873-4324 ; 0003-2670
ISSN (online)	1873-4324
ISSN	0003-2670
DOI	10.1016/j.aca.2013.09.023
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Article ; Online: The European AntibotABE Framework Program and Its Update: Development of Innovative Botulinum Antibodies.

Rasetti-Escargueil, Christine / Avril, Arnaud / Miethe, Sebastian / Mazuet, Christelle / Derman, Yagmur / Selby, Katja / Thullier, Philippe / Pelat, Thibaut / Urbain, Remi / Fontayne, Alexandre / Korkeala, Hannu / Sesardic, Dorothea / Hust, Michael / Popoff, Michel R

Toxins

2017 Volume 9, Issue 10

Abstract: The goal of the AntiBotABE Program was the development of recombinant antibodies that neutralize botulinum neurotoxins (BoNT) A, B and E. These serotypes are lethal and responsible for most human botulinum cases. To improve therapeutic efficacy, the ... ...

Abstract	The goal of the AntiBotABE Program was the development of recombinant antibodies that neutralize botulinum neurotoxins (BoNT) A, B and E. These serotypes are lethal and responsible for most human botulinum cases. To improve therapeutic efficacy, the heavy and light chains (HC and LC) of the three BoNT serotypes were targeted to achieve a synergistic effect (oligoclonal antibodies). For antibody isolation, macaques were immunized with the recombinant and non-toxic BoNT/A, B or E, HC or LC, followed by the generation of immune phage-display libraries. Antibodies were selected from these libraries against the holotoxin and further analyzed in in vitro and ex vivo assays. For each library, the best ex vivo neutralizing antibody fragments were germline-humanized and expressed as immunoglobulin G (IgGs). The IgGs were tested in vivo, in a standardized model of protection, and challenged with toxins obtained from collections of
MeSH term(s)	Animals ; Antibodies, Neutralizing/immunology ; Botulinum Toxins/immunology ; Humans ; Immunization ; Neurotoxins/immunology ; Recombinant Proteins/immunology ; Single-Chain Antibodies/immunology
Chemical Substances	Antibodies, Neutralizing ; Neurotoxins ; Recombinant Proteins ; Single-Chain Antibodies ; Botulinum Toxins (EC 3.4.24.69)
Language	English
Publishing date	2017--02
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins9100309
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Article ; Online: Capillary zone electrophoresis and capillary electrophoresis-mass spectrometry for analyzing qualitative and quantitative variations in therapeutic albumin.

Marie, Anne-Lise / Przybylski, Cédric / Gonnet, Florence / Daniel, Régis / Urbain, Rémi / Chevreux, Guillaume / Jorieux, Sylvie / Taverna, Myriam

Analytica chimica acta

2013 Volume 800, Page(s) 103–110

Abstract	The present study describes a reproducible and quantitative capillary zone electrophoresis (CZE) method, which leads to the separation of nine forms (native, oxidized and glycated) of human serum albumin (HSA). In an attempt to identify the different species separated by this CZE method, the capillary electrophoresis was coupled to mass spectrometry using a sheath liquid interface, an optimized capillary coating and a suitable CE running buffer. CE-MS analyses confirmed the heterogeneity of albumin preparation and revealed new truncated and modified forms such as Advanced Glycation End products (AGEs). Assignment of the CZE peaks was carried out using specific antibodies, carboxypeptidase A or sample reduction before or during the CE separation. Thus, five HSA forms were unambiguously identified. Using this CZE method several albumin batches produced by slightly different fractionation ways could be discriminated. Furthermore, analyses of HSA preparations marketed by five pharmaceutical industries revealed that two therapeutic albumins, including that marketed by LFB, contained the highest proportion of native form and lower levels of oxidized forms.
MeSH term(s)	Carboxypeptidases A/metabolism ; Electrophoresis, Capillary ; Glycation End Products, Advanced/analysis ; Humans ; Mass Spectrometry ; Oxidation-Reduction ; Serum Albumin/analysis ; Serum Albumin/metabolism
Chemical Substances	Glycation End Products, Advanced ; Serum Albumin ; Carboxypeptidases A (EC 3.4.17.1)
Language	English
Publishing date	2013-10-24
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1483436-4
ISSN	1873-4324 ; 0003-2670
ISSN (online)	1873-4324
ISSN	0003-2670
DOI	10.1016/j.aca.2013.09.023
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Article ; Online: Development of Germline-Humanized Antibodies Neutralizing Botulinum Neurotoxin A and B.

Miethe, Sebastian / Mazuet, Christelle / Liu, Yvonne / Tierney, Robert / Rasetti-Escargueil, Christine / Avril, Arnaud / Frenzel, André / Thullier, Philippe / Pelat, Thibaut / Urbain, Remi / Fontayne, Alexandre / Sesardic, Dorothea / Hust, Michael / Popoff, Michel Robert

PloS one

2016 Volume 11, Issue 8, Page(s) e0161446

Abstract: Botulinum neurotoxins (BoNTs) are counted among the most toxic substances known and are responsible for human botulism, a life-threatening disease characterized by flaccid muscle paralysis that occurs naturally by food poisoning or colonization of the ... ...

Abstract	Botulinum neurotoxins (BoNTs) are counted among the most toxic substances known and are responsible for human botulism, a life-threatening disease characterized by flaccid muscle paralysis that occurs naturally by food poisoning or colonization of the gastrointestinal tract by BoNT-producing clostridia. To date, 7 serologically distinct serotypes of BoNT (serotype A-G) are known. Due to the high toxicity of BoNTs the Centers for Disease Control and Prevention (CDC) have classified BoNTs as category A agent, including the six biological agents with the highest potential risk of use as bioweapons. Well tolerated antibodies neutralizing BoNTs are required to deal with the potential risk. In a previous work, we described the development of scFv and scFv-Fc (Yumab) from macaque origin (Macaca fascicularis) neutralizing BoNT/A and B by targeting the heavy and light chain of each serotype. In the present study, we humanized the macaque antibodies SEM120-IIIC1 (anti-BoNT/A light chain), A1HC38 (anti-BoNT/A heavy chain), BLC3 (anti-BoNT/B light chain) and B2-7 (anti-BoNT/B heavy chain) by germline-humanization to obtain a better potential immunotolerance in humans. We increased the Germinality Index (GI) of SEM120-IIIC1 to 94.5%, for A1HC38, to 95% for BLC3 and to 94.4% for B2-7. Furthermore, the neutralization efficacies of the germline-humanized antibodies were analyzed in lethal and non-lethal in vivo mouse assays as full IgG. The germline-humanized IgGs hu8SEM120-IIIC1, hu8A1HC38, hu8BLC3 and hu8B2-7 were protective in vivo, when anti-heavy and anti-light chain antibodies were combined. The synergistic effect and high humanness of the selected IgGs makes them promising lead candidates for further clinical development.
MeSH term(s)	Animals ; Antibodies, Monoclonal, Humanized/immunology ; Antibodies, Neutralizing/immunology ; Botulinum Toxins, Type A/immunology ; Botulism/immunology ; Clostridium botulinum ; Female ; Humans ; Immunoglobulin G/immunology ; Macaca fascicularis/immunology ; Mice ; Neutralization Tests ; Single-Chain Antibodies/immunology
Chemical Substances	Antibodies, Monoclonal, Humanized ; Antibodies, Neutralizing ; Immunoglobulin G ; Single-Chain Antibodies ; rimabotulinumtoxinB (0Y70779M1F) ; Botulinum Toxins, Type A (EC 3.4.24.69)
Language	English
Publishing date	2016-08-25
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0161446
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Article ; Online: Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody.

Derman, Yağmur / Selby, Katja / Miethe, Sebastian / Frenzel, André / Liu, Yvonne / Rasetti-Escargueil, Christine / Avril, Arnaud / Pelat, Thibaut / Urbain, Remi / Fontayne, Alexandre / Thullier, Philippe / Sesardic, Dorothea / Lindström, Miia / Hust, Michael / Korkeala, Hannu

Toxins

2016 Volume 8, Issue 9

Abstract: Botulinum neurotoxins (BoNTs) cause botulism and are the deadliest naturally-occurring substances known to humans. BoNTs have been classified as one of the category A agents by the Centers for Disease Control and Prevention, indicating their potential ... ...

Abstract	Botulinum neurotoxins (BoNTs) cause botulism and are the deadliest naturally-occurring substances known to humans. BoNTs have been classified as one of the category A agents by the Centers for Disease Control and Prevention, indicating their potential use as bioweapons. To counter bio-threat and naturally-occurring botulism cases, well-tolerated antibodies by humans that neutralize BoNTs are relevant. In our previous work, we showed the neutralizing potential of macaque (Macaca fascicularis)-derived scFv-Fc (scFv-Fc ELC18) by in vitro endopeptidase immunoassay and ex vivo mouse phrenic nerve-hemidiaphragm assay by targeting the light chain of the botulinum neurotoxin type E (BoNT/E). In the present study, we germline-humanized scFv-Fc ELC18 into a full IgG hu8ELC18 to increase its immunotolerance by humans. We demonstrated the protection and prophylaxis capacity of hu8ELC18 against BoNT/E in a mouse model. A concentration of 2.5 ng/mouse of hu8ELC18 protected against 5 mouse lethal dose (MLD) in a mouse protection assay and complete neutralization of 1 LD50 of pure BoNT/E toxin was achieved with 8 ng of hu8ELC18 in mouse paralysis assay. Furthermore, hu8ELC18 protected mice from 5 MLD if injected up to 14 days prior to intraperitoneal BoNT/E administration. This newly-developed humanized IgG is expected to have high tolerance in humans.
MeSH term(s)	Animals ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Neutralizing/pharmacology ; Antidotes/pharmacology ; Antitoxins/pharmacology ; Botulinum Toxins/antagonists & inhibitors ; Botulinum Toxins/immunology ; Botulism/immunology ; Botulism/microbiology ; Botulism/prevention & control ; Clostridium botulinum/drug effects ; Clostridium botulinum/immunology ; Clostridium botulinum/metabolism ; Disease Models, Animal ; Female ; Mice ; Single-Chain Antibodies/pharmacology
Chemical Substances	Antibodies, Monoclonal, Humanized ; Antibodies, Neutralizing ; Antidotes ; Antitoxins ; Single-Chain Antibodies ; Botulinum Toxins (EC 3.4.24.69) ; botulinum toxin type E (T579M564JY)
Language	English
Publishing date	2016--12
Publishing country	Switzerland
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins8090257
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